title: Formation kinetics and structural features of Beta-amyloid aggregates by sedimented solute NMR.
abstract: The accumulation of soluble toxic beta-amyloid (Aβ) aggregates is an attractive hypothesis for the role of this peptide in the pathology of Alzheimer's disease. We have introduced sedimentation through ultracentrifugation, either by magic angle spinning (in situ) or preparative ultracentrifuge (ex situ), to immobilize biomolecules and make them amenable for solid-state NMR studies (SedNMR). In situ SedNMR is used here to address the kinetics of formation of soluble Aβ assemblies by monitoring the disappearance of the monomer and the appearance of the oligomers simultaneously. Ex situ SedNMR allows us to select different oligomeric species and to reveal atomic-level structural features of soluble Aβ assemblies.
authors.affiliation: Magnetic Resonance Center (CERM), University of Florence, Via L. Sacconi 6, 50019 Sesto Fiorentino (Italy); Giotto Biotech, Via Madonna del Piano 6, 50019 Sesto Fiorentino (Italy); Fondazione Farmacogenomica FiorGen onlus Via L. Sacconi 6, 50019 Sesto Fiorentino (Italy).
authors.forename: Ivano
authors.initials: I
authors.lastname: Bertini
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gallo
authors.forename: Magdalena
authors.initials: M
authors.lastname: Korsak
authors.forename: Claudio
authors.initials: C
authors.lastname: Luchinat
authors.forename: Jiafei
authors.initials: J
authors.lastname: Mao
authors.forename: Enrico
authors.initials: E
authors.lastname: Ravera
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary; D012996:Solutions / Q000737:chemistry; D013696:Temperature; D014461:Ultracentrifugation
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D012996:Solutions; C075222:amyloid beta-protein (1-42)
keywords: centrifugation; kinetics; oligomerization; sedimentation; solid-state NMR spectroscopy